— Cervical intraepithelial neoplasia/HSIL. A) CIN 3 (high grade)/HSIL in a patient with HPV type 16 infection showing abnormal maturation and dysplastic cells with pleomorphic nuclei occupying the full thickness of the epithelium (left lower half), normal epithelium (right upper half). (HE, ×5). B) Immunohistological dual staining reveals specific cytoplasmic and nuclear p16 reaction (brown). Ki67 (red nuclei) marks proliferating cells where co-expression with p16 indicates a positive test result (see arrowhead) (×20). C) CIN 2 (intermediate grade)/HSIL in a patient with HPV type 59 infection with moderately dysplastic cells occupying the middle third of the epithelium. (HE, ×20). D) These cells show positive p16 immunostaining and the Ki67 proliferation zone is shifted towards the middle third (left half) which in normal epithelium is restricted to the basal cell layer (right half) (×20).